Skip to main content
SpringerLink
Log in
Book cover

Pain Control pp 261–284Cite as

Amygdala Pain Mechanisms

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 227))

Abstract

A limbic brain area, the amygdala plays a key role in emotional responses and affective states and disorders such as learned fear, anxiety, and depression. The amygdala has also emerged as an important brain center for the emotional–affective dimension of pain and for pain modulation. Hyperactivity in the laterocapsular division of the central nucleus of the amygdala (CeLC, also termed the “nociceptive amygdala”) accounts for pain-related emotional responses and anxiety-like behavior. Abnormally enhanced output from the CeLC is the consequence of an imbalance between excitatory and inhibitory mechanisms. Impaired inhibitory control mediated by a cluster of GABAergic interneurons in the intercalated cell masses (ITC) allows the development of glutamate- and neuropeptide-driven synaptic plasticity of excitatory inputs from the brainstem (parabrachial area) and from the lateral–basolateral amygdala network (LA-BLA, site of integration of polymodal sensory information). BLA hyperactivity also generates abnormally enhanced feedforward inhibition of principal cells in the medial prefrontal cortex (mPFC), a limbic cortical area that is strongly interconnected with the amygdala. Pain-related mPFC deactivation results in cognitive deficits and failure to engage cortically driven ITC-mediated inhibitory control of amygdala processing. Impaired cortical control allows the uncontrolled persistence of amygdala pain mechanisms.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

BLA:

Basolateral amygdala

CB1:

Cannabinoid receptor 1

CeA:

Central nucleus of the amygdala

CeLC:

Laterocapsular division of the central nucleus of the amygdala

ITC:

Intercalated cell mass

LA:

Lateral amygdala

mGluR:

Metabotropic glutamate receptor

mPFC:

Medial prefrontal cortex

NPS:

Neuropeptide S

PB:

Parabrachial area

References

  • Adedoyin MO, Vicini S, Neale JH (2010) Endogenous N-acetylaspartylglutamate (NAAG) inhibits synaptic plasticity/transmission in the amygdala in a mouse inflammatory pain model. Mol Pain 6:60–77

    PubMed Central  PubMed  Google Scholar 

  • Amir A, Amano T, Pare D (2011) Physiological identification and infralimbic responsiveness of rat intercalated amygdala neurons. J Neurophysiol 105:3054–3066

    PubMed Central  PubMed  Google Scholar 

  • Ansah OB, Bourbia N, Goncalves L, Almeida A, Pertovaara A (2010) Influence of amygdaloid glutamatergic receptors on sensory and emotional pain-related behavior in the neuropathic rat. Behav Brain Res 209:174–178

    CAS  PubMed  Google Scholar 

  • Apkarian AV, Neugebauer V, Koob G, Edwards S, Levine JD, Ferrari L, Egli M, Regunathan S (2013) Neural mechanisms of pain and alcohol dependence. Pharmacol Biochem Behav 112C:34–41

    Google Scholar 

  • Asan E, Yilmazer-Hanke DM, Eliava M, Hantsch M, Lesch KP, Schmitt A (2005) The corticotropin-releasing factor (CRF)-system and monoaminergic afferents in the central amygdala: investigations in different mouse strains and comparison with the rat. Neuroscience 131:953–967

    CAS  PubMed  Google Scholar 

  • Bale TL, Vale WW (2004) CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol 44:525–557

    CAS  PubMed  Google Scholar 

  • Baliki MN, Geha PY, Jabakhanji R, Harden N, Schnitzer TJ, Apkarian AV (2008) A preliminary fMRI study of analgesic treatment in chronic back pain and knee osteoarthritis. Mol Pain 4:47

    PubMed Central  PubMed  Google Scholar 

  • Bie B, Zhu W, Pan ZZ (2009) Rewarding morphine-induced synaptic function of delta-opioid receptors on central glutamate synapses. J Pharmacol Exp Ther 329:290–296

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bie B, Wang Y, Cai YQ, Zhang Z, Hou YY, Pan ZZ (2012) Upregulation of nerve growth factor in central amygdala increases sensitivity to opioid reward. Neuropsychopharmacology 37:2780–2788

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bird GC, Lash LL, Han JS, Zou X, Willis WD, Neugebauer V (2005) Protein kinase A-dependent enhanced NMDA receptor function in pain-related synaptic plasticity in rat amygdala neurones. J Physiol 564:907–921

    PubMed Central  CAS  PubMed  Google Scholar 

  • Blank T, Nijholt I, Grammatopoulos DK, Randeva HS, Hillhouse EW, Spiess J (2003) Corticotropin-releasing factor receptors couple to multiple G-proteins to activate diverse intracellular signaling pathways in mouse hippocampus: role in neuronal excitability and associative learning. J Neurosci 23:700–707

    CAS  PubMed  Google Scholar 

  • Bourbia N, Ansah OB, Pertovaara A (2010) Corticotropin-releasing factor in the rat amygdala differentially influences sensory-discriminative and emotional-like pain response in peripheral neuropathy. J Pain 11:1461–1471

    CAS  PubMed  Google Scholar 

  • Bourgeais L, Gauriau C, Bernard J-F (2001) Projections from the nociceptive area of the central nucleus of the amygdala to the forebrain: a PHA-L study in the rat. Eur J Neurosci 14:229–255

    CAS  PubMed  Google Scholar 

  • Busti D, Geracitano R, Whittle N, Dalezios Y, Manko M, Kaufmann W, Satzler K, Singewald N, Capogna M, Ferraguti F (2011) Different fear states engage distinct networks within the intercalated cell clusters of the amygdala. J Neurosci 31:5131–5144

    CAS  PubMed  Google Scholar 

  • Cai YQ, Wang W, Hou YY, Zhang Z, Xie J, Pan ZZ (2013) Central amygdala GluA1 facilitates associative learning of opioid reward. J Neurosci 33:1577–1588

    PubMed Central  CAS  PubMed  Google Scholar 

  • Carrasquillo Y, Gereau RW (2007) Activation of the extracellular signal-regulated kinase in the amygdala modulates pain perception. J Neurosci 27:1543–1551

    CAS  PubMed  Google Scholar 

  • Carrasquillo Y, Gereau RW (2008) Hemispheric lateralization of a molecular signal for pain modulation in the amygdala. Mol Pain 4:24

    PubMed Central  PubMed  Google Scholar 

  • Charney DS (2003) Neuroanatomical circuits modulating fear and anxiety behaviors. Acta Psychiatr Scand Suppl (417):38–50

    Google Scholar 

  • Commons KG, Connolley KR, Valentino RJ (2003) A neurochemically distinct dorsal raphe-limbic circuit with a potential role in affective disorders. Neuropsychopharmacology 28:206–215

    CAS  PubMed  Google Scholar 

  • Crock LW, Kolber BJ, Morgan CD, Sadler KE, Vogt SK, Bruchas MR, Gereau RW (2012) Central amygdala metabotropic glutamate receptor 5 in the modulation of visceral pain. J Neurosci 32:14217–14226

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dalley JW, Everitt BJ, Robbins TW (2011) Impulsivity, compulsivity, and top-down cognitive control. Neuron 69:680–694

    CAS  PubMed  Google Scholar 

  • de Lacalle S, Saper CB (2000) Calcitonin gene-related peptide-like immunoreactivity marks putative visceral sensory pathways in human brain. Neuroscience 100:115–130

    PubMed  Google Scholar 

  • Dobolyi A, Irwin S, Makara G, Usdin TB, Palkovits M (2005) Calcitonin gene-related peptide-containing pathways in the rat forebrain. J Comp Neurol 489:92–119

    CAS  PubMed  Google Scholar 

  • Ferraguti F, Crepaldi L, Nicoletti F (2008) Metabotropic glutamate 1 receptor: current concepts and perspectives. Pharmacol Rev 60:536–581

    CAS  PubMed  Google Scholar 

  • Fields HL (2000) Pain modulation: expectation, opioid analgesia and virtual pain. Prog Brain Res 122:245–253

    CAS  PubMed  Google Scholar 

  • Fu Y, Neugebauer V (2008) Differential mechanisms of CRF1 and CRF2 receptor functions in the amygdala in pain-related synaptic facilitation and behavior. J Neurosci 28:3861–3876

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fu Y, Han J, Ishola T, Scerbo M, Adwanikar H, Ramsey C, Neugebauer V (2008) PKA and ERK, but not PKC, in the amygdala contribute to pain-related synaptic plasticity and behavior. Mol Pain 4:26–46

    PubMed Central  PubMed  Google Scholar 

  • Gauriau C, Bernard J-F (2002) Pain pathways and parabrachial circuits in the rat. Exp Physiol 87(2):251–258

    PubMed  Google Scholar 

  • Goncalves L, Dickenson AH (2012) Asymmetric time-dependent activation of right central amygdala neurones in rats with peripheral neuropathy and pregabalin modulation. Eur J Neurosci 36:3204–3213

    PubMed  Google Scholar 

  • Gray TS (1993) Amygdaloid CRF pathways. Role in autonomic, neuroendocrine, and behavioral responses to stress. Ann N Y Acad Sci 697:53–60

    CAS  PubMed  Google Scholar 

  • Greenwood-Van Meerveld B, Johnson AC, Schulkin J, Myers DA (2006) Long-term expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus in response to an acute colonic inflammation. Brain Res 1071:91–96

    CAS  PubMed  Google Scholar 

  • Guerrini R, Salvadori S, Rizzi A, Regoli D, Calo’ G (2010) Neurobiology, pharmacology, and medicinal chemistry of neuropeptide S and its receptor. Med Res Rev 30:751–777

    CAS  PubMed  Google Scholar 

  • Han JS, Neugebauer V (2004) Synaptic plasticity in the amygdala in a visceral pain model in rats. Neurosci Lett 361:254–257

    CAS  PubMed  Google Scholar 

  • Han JS, Neugebauer V (2005) mGluR1 and mGluR5 antagonists in the amygdala inhibit different components of audible and ultrasonic vocalizations in a model of arthritic pain. Pain 113:211–222

    CAS  PubMed  Google Scholar 

  • Han JS, Bird GC, Neugebauer V (2004) Enhanced group III mGluR-mediated inhibition of pain-related synaptic plasticity in the amygdala. Neuropharmacology 46:918–926

    CAS  PubMed  Google Scholar 

  • Han JS, Li W, Neugebauer V (2005) Critical role of calcitonin gene-related peptide 1 receptors in the amygdala in synaptic plasticity and pain behavior. J Neurosci 25:10717–10728

    CAS  PubMed  Google Scholar 

  • Han JS, Fu Y, Bird GC, Neugebauer V (2006) Enhanced group II mGluR-mediated inhibition of pain-related synaptic plasticity in the amygdala. Mol Pain 2:18–29

    PubMed Central  PubMed  Google Scholar 

  • Han JS, Adwanikar H, Li Z, Ji G, Neugebauer V (2010) Facilitation of synaptic transmission and pain responses by CGRP in the amygdala of normal rats. Mol Pain 6:10–23

    PubMed Central  PubMed  Google Scholar 

  • Harrigan EA, Magnuson DJ, Thunstedt GM, Gray TS (1994) Corticotropin releasing factor neurons are innervated by calcitonin gene-related peptide terminals in the rat central amygdaloid nucleus. Brain Res Bull 33:529–534

    CAS  PubMed  Google Scholar 

  • Hauger RL, Risbrough V, Oakley RH, Olivares-Reyes JA, Dautzenberg FM (2009) Role of CRF receptor signaling in stress vulnerability, anxiety, and depression. Ann N Y Acad Sci 1179:120–143

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hay DL (2007) What makes a CGRP2 receptor? Clin Exp Pharmacol Physiol 34:963–971

    CAS  PubMed  Google Scholar 

  • Hebert MA, Ardid D, Henrie JA, Tamashiro K, Blanchard DC, Blanchard RJ (1999) Amygdala lesions produce analgesia in a novel, ethologically relevant acute pain test. Physiol Behav 67(1):99–105

    CAS  PubMed  Google Scholar 

  • Herry C, Ferraguti F, Singewald N, Letzkus JJ, Ehrlich I, Luthi A (2010) Neuronal circuits of fear extinction. Eur J Neurosci 31:599–612

    PubMed  Google Scholar 

  • Holland PC, Gallagher M (2004) Amygdala-frontal interactions and reward expectancy. Curr Opin Neurobiol 14:148–155

    CAS  PubMed  Google Scholar 

  • Ikeda R, Takahashi Y, Inoue K, Kato F (2007) NMDA receptor-independent synaptic plasticity in the central amygdala in the rat model of neuropathic pain. Pain 127:161–172

    CAS  PubMed  Google Scholar 

  • Ji G, Neugebauer V (2007) Differential effects of CRF1 and CRF2 receptor antagonists on pain-related sensitization of neurons in the central nucleus of the amygdala. J Neurophysiol 97:3893–3904

    CAS  PubMed  Google Scholar 

  • Ji G, Neugebauer V (2008) Pro- and anti-nociceptive effects of corticotropin-releasing factor (CRF) in central amygdala neurons are mediated through different receptors. J Neurophysiol 99:1201–1212

    CAS  PubMed  Google Scholar 

  • Ji G, Neugebauer V (2009) Hemispheric lateralization of pain processing by amygdala neurons. J Neurophysiol 1102:2253–2264

    Google Scholar 

  • Ji G, Neugebauer V (2010) Reactive oxygen species are involved in group I mGluR-mediated facilitation of nociceptive processing in amygdala neurons. J Neurophysiol 104:218–229

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ji G, Neugebauer V (2011) Pain-related deactivation of medial prefrontal cortical neurons involves mGluR1 and GABAA receptors. J Neurophysiol 106:2642–2652

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ji G, Fu Y, Ruppert KA, Neugebauer V (2007) Pain-related anxiety-like behavior requires CRF1 receptors in the amygdala. Mol Pain 3:13–17

    PubMed Central  PubMed  Google Scholar 

  • Ji G, Horvath C, Neugebauer V (2009) NR2B receptor blockade inhibits pain-related sensitization of amygdala neurons. Mol Pain 5:21–26

    PubMed Central  PubMed  Google Scholar 

  • Ji G, Sun H, Fu Y, Li Z, Pais-Vieira M, Galhardo V, Neugebauer V (2010) Cognitive impairment in pain through amygdala-driven prefrontal cortical deactivation. J Neurosci 30:5451–5464

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ji G, Fu Y, Adwanikar H, Neugebauer V (2013) Non-pain-related CRF1 activation in the amygdala facilitates synaptic transmission and pain responses. Mol Pain 9:2

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jongen-Relo AL, Amaral DG (1998) Evidence for a GABAergic projection from the central nucleus of the amygdala to the brainstem of the macaque monkey: a combined retrograde tracing and in situ hybridization study. Eur J Neurosci 10:2924–2933

    CAS  PubMed  Google Scholar 

  • Jungling K, Seidenbecher T, Sosulina L, Lesting J, Sangha S, Clark SD, Okamura N, Duangdao DM, Xu YL, Reinscheid RK, Pape HC (2008) Neuropeptide S-mediated control of fear expression and extinction: role of intercalated GABAergic neurons in the amygdala. Neuron 59:298–310

    PubMed Central  PubMed  Google Scholar 

  • Kolber BJ, Montana MC, Carrasquillo Y, Xu J, Heinemann SF, Muglia LJ, Gereau RW (2010) Activation of metabotropic glutamate receptor 5 in the amygdala modulates pain-like behavior. J Neurosci 30:8203–8213

    PubMed Central  CAS  PubMed  Google Scholar 

  • Koob GF (2010) The role of CRF and CRF-related peptides in the dark side of addiction. Brain Res 1314:3–14

    CAS  PubMed  Google Scholar 

  • Kruger L, Sternini C, Brecha NC, Mantyh PW (1988) Distribution of calcitonin gene-related peptide immunoreactivity in relation to the rat central somatosensory projection. J Comp Neurol 273:149–162

    CAS  PubMed  Google Scholar 

  • Kulkarni B, Bentley DE, Elliott R, Julyan PJ, Boger E, Watson A, Boyle Y, El-Deredy W, Jones AK (2007) Arthritic pain is processed in brain areas concerned with emotions and fear. Arthritis Rheum 56:1345–1354

    CAS  PubMed  Google Scholar 

  • Laviolette SR, Grace AA (2006) Cannabinoids potentiate emotional learning plasticity in neurons of the medial prefrontal cortex through basolateral amygdala inputs. J Neurosci 26:6458–6468

    CAS  PubMed  Google Scholar 

  • Leonard SK, Ring RH (2011) Immunohistochemical localization of the neuropeptide S receptor in the rat central nervous system. Neuroscience 172:153–163

    CAS  PubMed  Google Scholar 

  • Li W, Neugebauer V (2004a) Block of NMDA and non-NMDA receptor activation results in reduced background and evoked activity of central amygdala neurons in a model of arthritic pain. Pain 110:112–122

    CAS  PubMed  Google Scholar 

  • Li W, Neugebauer V (2004b) Differential roles of mGluR1 and mGluR5 in brief and prolonged nociceptive processing in central amygdala neurons. J Neurophysiol 91:13–24

    CAS  PubMed  Google Scholar 

  • Li W, Neugebauer V (2006) Differential changes of group II and group III mGluR function in central amygdala neurons in a model of arthritic pain. J Neurophysiol 96:1803–1815

    CAS  PubMed  Google Scholar 

  • Li N, Liang J, Fang CY, Han HR, Ma MS, Zhang GX (2008) Involvement of CGRP and CGRPl receptor in nociception in the basolateral nucleus of amygdala of rats. Neurosci Lett 443:184–187

    CAS  PubMed  Google Scholar 

  • Li W, Chang M, Peng YL, Gao YH, Zhang JN, Han RW, Wang R (2009) Neuropeptide S produces antinociceptive effects at the supraspinal level in mice. Regul Pept 156:90–95

    PubMed  Google Scholar 

  • Li Z, Ji G, Neugebauer V (2011) Mitochondrial reactive oxygen species are activated by mGluR5 through IP3 and activate ERK and PKA to increase excitability of amygdala neurons and pain behavior. J Neurosci 31:1114–1127

    PubMed Central  CAS  PubMed  Google Scholar 

  • Likhtik E, Popa D, Apergis-Schoute J, Fidacaro GA, Pare D (2008) Amygdala intercalated neurons are required for expression of fear extinction. Nature 454:642–645

    PubMed Central  CAS  PubMed  Google Scholar 

  • Liu CC, Ohara S, Franaszczuk P, Zagzoog N, Gallagher M, Lenz FA (2010) Painful stimuli evoke potentials recorded from the medial temporal lobe in humans. Neuroscience 165:1402–1411

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ma W, Chabot J-G, Powell KJ, Jhamandas K, Dickerson IM, Quirion R (2003) Localization and modulation of calcitonin gene-related peptide-receptor component protein-immunoreactive cells in the rat central and peripheral nervous systems. Neuroscience 120:677–694

    CAS  PubMed  Google Scholar 

  • Manning BH (1998) A lateralized deficit in morphine antinociception after unilateral inactivation of the central amygdala. J Neurosci 18:9453–9470

    CAS  PubMed  Google Scholar 

  • Manning BH, Mayer DJ (1995a) The central nucleus of the amygdala contributes to the production of morphine antinociception in the formalin test. Pain 63:141–152

    CAS  PubMed  Google Scholar 

  • Manning BH, Mayer DJ (1995b) The central nucleus of the amygdala contributes to the production of morphine antinociception in the rat tail-flick test. J Neurosci 15(12):8199–8213

    CAS  PubMed  Google Scholar 

  • Marek R, Strobel C, Bredy TW, Sah P (2013) The amygdala and medial prefrontal cortex: partners in the fear circuit. J Physiol 591:2381–2391

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mason P (2005) Deconstructing endogenous pain modulations. J Neurophysiol 94:1659–1663

    CAS  PubMed  Google Scholar 

  • McDonald AJ (1998) Cortical pathways to the mammalian amygdala. Prog Neurobiol 55:257–332

    CAS  PubMed  Google Scholar 

  • McGaugh JL (2004) The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annu Rev Neurosci 27:1–28

    CAS  PubMed  Google Scholar 

  • McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, Foord SM (1998) RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393:333–339

    CAS  PubMed  Google Scholar 

  • McNally GP, Akil H (2002) Role of corticotropin-releasing hormone in the amygdala and bed nucleus of the stria terminalis in the behavioral, pain modulatory, and endocrine consequences of opiate withdrawal. Neuroscience 112:605–617

    CAS  PubMed  Google Scholar 

  • Myers B, Greenwood-Van Meerveld B (2010) Divergent effects of amygdala glucocorticoid and mineralocorticoid receptors in the regulation of visceral and somatic pain. Am J Physiol Gastrointest Liver Physiol 298:G295–G303

    CAS  PubMed  Google Scholar 

  • Myers DA, Gibson M, Schulkin J, Greenwood Van-Meerveld B (2005) Corticosterone implants to the amygdala and type 1 CRH receptor regulation: effects on behavior and colonic sensitivity. Behav Brain Res 161:39–44

    CAS  PubMed  Google Scholar 

  • Nakao A, Takahashi Y, Nagase M, Ikeda R, Kato F (2012) Role of capsaicin-sensitive C-fiber afferents in neuropathic pain-induced synaptic potentiation in the nociceptive amygdala. Mol Pain 8:51

    PubMed Central  CAS  PubMed  Google Scholar 

  • Neugebauer V, Li W (2003) Differential sensitization of amygdala neurons to afferent inputs in a model of arthritic pain. J Neurophysiol 89:716–727

    PubMed  Google Scholar 

  • Neugebauer V, Zinebi F, Russell R, Gallagher JP, Shinnick-Gallagher P (2000) Cocaine and kindling alter the sensitivity of group II and III metabotropic glutamate receptors in the central amygdala. J Neurophysiol 84:759–770

    CAS  PubMed  Google Scholar 

  • Neugebauer V, Li W, Bird GC, Bhave G, Gereau RW (2003) Synaptic plasticity in the amygdala in a model of arthritic pain: differential roles of metabotropic glutamate receptors 1 and 5. J Neurosci 23:52–63

    CAS  PubMed  Google Scholar 

  • Neugebauer V, Li W, Bird GC, Han JS (2004) The amygdala and persistent pain. Neuroscientist 10:221–234

    PubMed  Google Scholar 

  • Neugebauer V, Galhardo V, Maione S, Mackey SC (2009) Forebrain pain mechanisms. Brain Res Rev 60:226–242

    PubMed Central  PubMed  Google Scholar 

  • Nicoletti F, Bockaert J, Collingridge GL, Conn PJ, Ferraguti F, Schoepp DD, Wroblewski JT, Pin JP (2011) Metabotropic glutamate receptors: from the workbench to the bedside. Neuropharmacology 60:1017–1041

    PubMed Central  CAS  PubMed  Google Scholar 

  • Niswender CM, Conn PJ (2010) Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 50:295–322

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ochsner KN, Gross JJ (2005) The cognitive control of emotion. Trends Cogn Sci 9:242–249

    PubMed  Google Scholar 

  • Oliver KR, Kane SA, Salvatore CA, Mallee JJ, Kinsey AM, Koblan KS, Keyvan-Fouladi N, Heavens RP, Wainwright A, Jacobson M, Dickerson IM, Hill RG (2001) Cloning, characterization and central nervous system distribution of receptor activity modifying proteins in the rat. Eur J Neurosci 14:618–628

    CAS  PubMed  Google Scholar 

  • Orsini CA, Maren S (2012) Neural and cellular mechanisms of fear and extinction memory formation. Neurosci Biobehav Rev 36:1773–1802

    PubMed Central  PubMed  Google Scholar 

  • Palazzo E, Fu Y, Ji G, Maione S, Neugebauer V (2008) Group III mGluR7 and mGluR8 in the amygdala differentially modulate nocifensive and affective pain behaviors. Neuropharmacology 55:537–545

    PubMed Central  CAS  PubMed  Google Scholar 

  • Palazzo E, Marabese I, Soukupova M, Luongo L, Boccella S, Giordano C, de Novellis V, Rossi F, Maione S (2011) Metabotropic glutamate receptor subtype 8 in the amygdala modulates thermal threshold, neurotransmitter release, and rostral ventromedial medulla cell activity in inflammatory pain. J Neurosci 31:4687–4697

    CAS  PubMed  Google Scholar 

  • Pape HC, Pare D (2010) Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol Rev 90:419–463

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pedersen LH, Scheel-Kruger J, Blackburn-Munro G (2007) Amygdala GABA-A receptor involvement in mediating sensory-discriminative and affective-motivational pain responses in a rat model of peripheral nerve injury. Pain 127:17–26

    CAS  PubMed  Google Scholar 

  • Peng YL, Zhang JN, Chang M, Li W, Han RW, Wang R (2010) Effects of central neuropeptide S in the mouse formalin test. Peptides 31:1878–1883

    CAS  PubMed  Google Scholar 

  • Pinard CR, Mascagni F, McDonald AJ (2012) Medial prefrontal cortical innervation of the intercalated nuclear region of the amygdala. Neuroscience 205:112–124

    CAS  PubMed  Google Scholar 

  • Poyner DR, Sexton PM, Marshall I, Smith DM, Quirion R, Born W, Muff R, Fischer JA, Foord SM (2002) International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev 54:233–246

    CAS  PubMed  Google Scholar 

  • Price JL (2003) Comparative aspects of amygdala connectivity. In: Shinnick-Gallagher P, Pitkanen A, Shekhar A, Cahill L (eds) The amygdala in brain function. Basic and clinical approaches, vol 985. The New York Academy of Sciences, New York, pp 50–58

    Google Scholar 

  • Qin C, Greenwood-Van Meerveld B, Foreman RD (2003) Visceromotor and spinal neuronal responses to colorectal distension in rats with aldosterone onto the amygdala. J Neurophysiol 90:2–11

    CAS  PubMed  Google Scholar 

  • Rea K, Lang Y, Finn DP (2009) Alterations in extracellular levels of gamma-aminobutyric acid in the rat basolateral amygdala and periaqueductal gray during conditioned fear, persistent pain and fear-conditioned analgesia. J Pain 10:1088–1098

    CAS  PubMed  Google Scholar 

  • Reinscheid RK (2008) Neuropeptide S: anatomy, pharmacology, genetics and physiological functions. Results Probl Cell Differ 46:145–158

    CAS  PubMed  Google Scholar 

  • Ren W, Neugebauer V (2010) Pain-related increase of excitatory transmission and decrease of inhibitory transmission in the central nucleus of the amygdala are mediated by mGluR1. Mol Pain 6:93–106

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ren W, Palazzo E, Maione S, Neugebauer V (2011) Differential effects of mGluR7 and mGluR8 activation on pain-related synaptic activity in the amygdala. Neuropharmacology 61:1334–1344

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ren W, Kiritoshi T, Gregoire S, Ji G, Guerrini R, Calo G, Neugebauer V (2013) Neuropeptide S: a novel regulator of pain-related amygdala plasticity and behaviors. J Neurophysiol 110:1765–1781

    PubMed Central  CAS  PubMed  Google Scholar 

  • Reul JM, Holsboer F (2002) Corticotropin-releasing factor receptors 1 and 2 in anxiety and depression. Curr Opin Pharmacol 2:23–33

    CAS  PubMed  Google Scholar 

  • Robinson SD, Aitken JF, Bailey RJ, Poyner DR, Hay DL (2009) Novel peptide antagonists of adrenomedullin and calcitonin gene-related peptide receptors: identification, pharmacological characterization, and interactions with position 74 in receptor activity-modifying protein 1/3. J Pharmacol Exp Ther 331:513–521

    CAS  PubMed  Google Scholar 

  • Rouwette T, Vanelderen P, Reus MD, Loohuis NO, Giele J, van Egmond J, Scheenen W, Scheffer GJ, Roubos E, Vissers K, Kozicz T (2011) Experimental neuropathy increases limbic forebrain CRF. Eur J Pain 16(1):61–71

    Google Scholar 

  • Ruzza C, Pulga A, Rizzi A, Marzola G, Guerrini R, Calo’ G (2012) Behavioural phenotypic characterization of CD-1 mice lacking the neuropeptide S receptor. Neuropharmacology 62:1999–2009

    CAS  PubMed  Google Scholar 

  • Sanchez MM, Young LJ, Plotsky PM, Insel TR (1999) Autoradiographic and in situ hybridization localization of corticotropin-releasing factor 1 and 2 receptors in nonhuman primate brain. J Comp Neurol 408(3):365–377

    CAS  PubMed  Google Scholar 

  • Schiess MC, Callahan PM, Zheng H (1999) Characterization of the electrophysiological and morphological properties of rat central amygdala neurons in vitro. J Neurosci Res 58:663–673

    CAS  PubMed  Google Scholar 

  • Schwaber JS, Sternini C, Brecha NC, Rogers WT, Card JP (1988) Neurons containing calcitonin gene-related peptide in the parabrachial nucleus project to the central nucleus of the amygdala. J Comp Neurol 270:416–426

    CAS  PubMed  Google Scholar 

  • Simons LE, Moulton EA, Linnman C, Carpino E, Becerra L, Borsook D (2012) The human amygdala and pain: evidence from neuroimaging. Hum Brain Mapp 35(2):527–538. doi:10.1002/hbm.22199

    PubMed Central  PubMed  Google Scholar 

  • Sotres-Bayon F, Quirk GJ (2010) Prefrontal control of fear: more than just extinction. Curr Opin Neurobiol 20:231–235

    PubMed Central  CAS  PubMed  Google Scholar 

  • Spuz CA, Borszcz GS (2012) NMDA or non-NMDA receptor antagonism within the amygdaloid central nucleus suppresses the affective dimension of pain in rats: evidence for hemispheric synergy. J Pain 13:328–337

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sun N, Cassell MD (1993) Intrinsic GABAergic neurons in the rat central extended amygdala. J Comp Neurol 330:381–404

    CAS  PubMed  Google Scholar 

  • Tache Y, Bonaz B (2007) Corticotropin-releasing factor receptors and stress-related alterations of gut motor function. J Clin Invest 117:33–40

    PubMed Central  CAS  PubMed  Google Scholar 

  • Takahashi LK (2001) Role of CRF(1) and CRF(2) receptors in fear and anxiety. Neurosci Biobehav Rev 25:627–636

    CAS  PubMed  Google Scholar 

  • Tillisch K, Mayer EA, Labus JS (2010) Quantitative meta-analysis identifies brain regions activated during rectal distension in irritable bowel syndrome. Gastroenterology 140:91–100

    PubMed Central  PubMed  Google Scholar 

  • Ulrich-Lai YM, Xie W, Meij JTA, Dolgas CM, Yu L, Herman JP (2006) Limbic and HPA axis function in an animal model of chronic neuropathic pain. Physiol Behav 88:67–76

    CAS  PubMed  Google Scholar 

  • Uryu K, Okumura T, Shibasaki T, Sakanaka M (1992) Fine structure and possible origins of nerve fibers with corticotropin-releasing factor-like immunoreactivity in the rat central amygdaloid nucleus. Brain Res 577:175–179

    CAS  PubMed  Google Scholar 

  • Van Rossum D, Hanish U-K, Quirion R (1997) Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci Biobehav Rev 21:649–678

    PubMed  Google Scholar 

  • Wimalawansa SJ (1996) Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials. Endocr Rev 17:533–585

    CAS  PubMed  Google Scholar 

  • Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, Brucher FA, Zeng J, Ly NK, Henriksen SJ, De LL, Civelli O (2004) Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Neuron 43:487–497

    CAS  PubMed  Google Scholar 

  • Xu YL, Gall CM, Jackson VR, Civelli O, Reinscheid RK (2007) Distribution of neuropeptide S receptor mRNA and neurochemical characteristics of neuropeptide S-expressing neurons in the rat brain. J Comp Neurol 500:84–102

    CAS  PubMed  Google Scholar 

  • Zhang RX, Zhang M, Li A, Pan L, Berman BM, Ren K, Lao L (2013) DAMGO in the central amygdala alleviates the affective dimension of pain in a rat model of inflammatory hyperalgesia. Neuroscience 252:359–366

    CAS  PubMed  Google Scholar 

  • Zhu W, Pan ZZ (2004) Synaptic properties and postsynaptic opioid effects in rat central amygdala neurons. Neuroscience 127:871–879

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Work in the author’s lab is supported by National Institute of Neurological Disorders and Stroke Grants NS-081121, NS-38261, and NS-11255.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Neuroscience, Center for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430-6592, USA

    Volker Neugebauer

Authors
  1. Volker Neugebauer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Volker Neugebauer .

Editor information

Editors and Affiliations

  1. Institute of Physiology/Neurophysiology, Jena University Hospital, Jena, Thüringen, Germany

    Hans-Georg Schaible

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Neugebauer, V. (2015). Amygdala Pain Mechanisms. In: Schaible, HG. (eds) Pain Control. Handbook of Experimental Pharmacology, vol 227. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46450-2_13

Download citation

Publish with us

Policies and ethics

Search

Navigation